Calretinin (CR) is a calcium binding protein that is found in subpopulations of cortical and subcortical brain neurons. CR has been linked to neuroprotective functions both in vitro and in vivo in models of Parkinson's disease and several reports of Alzheimer's disease. Cortical atrophy, neuronal loss and glial pathology has been reported in patients with Acquired Immuno-Deficiency (AIDS). The envelope HIV viral glycoprotein, gp 120, induces the release of N-methyl-D-aspartate (NMDA)- like neurotoxins either directly or indirectly. This gp 120-induced toxicity can be blocked by either calcium or sodium channel blockers. Because of CR's potential calcium buffering capabilities and our recent finding that CR-containing neurons of the mesencephalon are resistant to excitotoxic damage (Isaacs et al., 1996), we decided to treat cortical cultures with gp 120. We will expose CR-containing neurons to various concentrations of gp 120 in E14 rat cortical cultures, and using immunofluorescent histochemistry we will compare the morphology of neurons which contain CR to those which have no CR. In addition to direct test to determine whether the presence of CR effects cell survival after gp 120 exposure, we will transfect immortal neuronal cell lines with plasmids coding for the fusion protein consisting of green fluorescent protein and CR, and examine their survival also.